Triethylamine → HCID 54474940, compound

HRID 1433004Notes

Reaction equation

HRID 1433004 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[CH:10]=[C:9]1[CH2:17][N:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]#[CH:26])[CH2:20][C:19]1=[O:27])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:28]([O:32][C:33](=[O:42])[NH:34][C:35]1[CH:40]=[CH:39][N:38]=[CH:37][C:36]=1I)([CH3:31])([CH3:30])[CH3:29].CCN(CC)CC>CN(C=O)C.CCOC(C)=O.O.[Cu]I>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[CH:10]=[C:9]1[CH2:17][N:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]#[C:26][C:40]2[CH:39]=[N:38][CH:37]=[CH:36][C:35]=2[NH:34][C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:42])[CH2:20][C:19]1=[O:27])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 10903275(3-Iodo-pyridin-4-yl)-carbamic acid tert-butyl esterHCID 53990821HCID 53990821, compound

Product 1

HCID 54474940HCID 54474940, compoundYield 51%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution containing 2-(2-oxo-4-prop-2-ynyl-piperazin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (100 mg, 0.27 mmol), EXAMPLE 743, (3-iodo-pyridin-4-yl)-carbamic acid tert-butyl ester (87 mg, 0.27 mmol), EXAMPLE 69, Part B, Et3N (110 mg, 1.08 mmol), (Ph3P)4PdCl2 (10 mg, 0.013 mmol), and CuI (1 mg, 0.008 mmol) in anhydrous DMF (5 mL) is stirred at ambient temperature. After 5 h, the reaction mixture is diluted with EtOAc (50 mL) and water (50 mL) and the layers are separated. The aqueous layer is extracted twice with EtOAc (25 mL) and the combined organic phase is washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude residue is purified by flash silica gel chromatography (CH2Cl2 to 10% MeOH CH2Cl2) to provide 77 mg (51%) of the title compound as a colorless oil. 1H NMR (300 MHz, CDCl3, ˜2:1 mixture of rotamers) major rotamer: δ1.53 (s, 9H), 1.69 (s, 9H), 2.98 (m, 2H), 3.49 (s, 2H), 3.56 (m, 2H), 3.78 (s, 2H), 4.98 (s, 2H), 6.43 (s, 1H), 7.89 (m, 1H), 8.09 (m, 2H), 8.34 (m, 1H), 8.41 (m, 1H), 8.75 (m, 1H) ppm; MS (ISP loop): m/z 561 (M+H).

Workup

  1. customthe layers are separated
  2. extractionThe aqueous layer is extracted twice with EtOAc (25 mL)
  3. washthe combined organic phase is washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue is purified by flash silica gel chromatography (CH2Cl2 to 10% MeOH CH2Cl2)

Sources & evidence

ORD record
ord-125e352c759e40dead9bc6eda7e74af9
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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